rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.47360/1995-4484-2024-435-440rsp-3613Research ArticleКЛИНИЧЕСКИЙ СЛУЧАЙCLINICAL OBSERVATIONОсобенности течения системного аутоиммунного заболевания, ассоциированного с антителами к Ku-антигену (описание двух клинических случаев)Features of systemic autoimmune disease associated with anti-Ku antibodies (descriptions of two clinical cases)https://orcid.org/0000-0001-8099-2107ТоргашинаА. В.TorgashinaAnna V.

Торгашина Анна Васильевна

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

anna.torgashina@gmail.comhttps://orcid.org/0000-0002-4804-3689Хелковская-СергееваА. Н.Khelkovskaya-SergeevaAnna N.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0009-0007-1444-5376АбдыкеримовА. О.AbdykerimovAskat O.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0002-0447-4110ХальметоваА. Р.KhalmetovaAlsu R.

115522, Москва, Каширское шоссе, 34а

115522, Moscow, Kashirskoye Highway, 34A

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian Federation202403092024624435–440Copyright © Торгашина А.В., Хелковская-Сергеева А.Н., Абдыкеримов А.О., Хальметова А.Р., 20242024Торгашина А.В., Хелковская-Сергеева А.Н., Абдыкеримов А.О., Хальметова А.Р.Torgashina A.V., Khelkovskaya-Sergeeva A.N., Abdykerimov A.O., Khalmetova A.R.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/3613

Антитела к Ku антигену (анти-Ku) – особый тип миозит-ассоциированных антител, характерных для пациентов с перекрестным синдромом системной склеродермии и иммуновоспалительной миопатии, а также встречающихся при других аутоиммунных заболеваниях. Пациенты с данными антителами имеют клиниколабораторные особенности заболевания.

Впервые в отечественной литературе представлены описания двух клинических случаев развития перекрестного синдрома, ассоциированного с анти-Ku. Проанализированы особенности течения заболевания и ответа на различные варианты иммуносупрессивной терапии.

Anti-Ku antibodies are a special type of myositis-associated antibodies that are characteristic of patients with the overlap syndrome of systemic scleroderma and immune-inflammatory myopathy, as well as occurring in other autoimmune diseases. Patients with these antibodies have their own clinical and laboratory features of the disease and can be identified as a separate anti-Ku syndrome.

For the first time in the domestic literature, descriptions of two clinical cases of the development of a cross syndrome associated with anti-Ku antibodies are presented. The features of the course of the disease and the response to various options for immunosuppressive therapy were analyzed.

анти-Ku антителаперекрестный синдромсистемная склеродермиясиндром Шегренамиозитинтерстициальное поражение легкихanti-Ku antibodiesoverlap syndromesclerodermaSjögren’s syndromemyositisinterstitial lung diseaseИсследование выполнено в рамках выполнения государственного задания по теме FURS-2022-003 (номер государ- ственного задания 1021051402790-6) «Изучение иммунопатологии, диагностики и терапии на ранних стадиях системных ревматических заболеваний».ReferencesTargoff IN. Laboratory testing in the diagnosis and management of idiopathic inflammatory myopathies. Rheum Dis Clin North Am. 2002;28:859-890.Targoff IN. Laboratory testing in the diagnosis and management of idiopathic inflammatory myopathies. Rheum Dis Clin North Am. 2002;28:859-890.Casal-Dominguez M, Pinal-Fernandez I, Derfoul A, Graf R, Michelle H, Albayda J, et al. The phenotype of myositis patients with anti-Ku autoantibodies. Semin Arthritis Rheum. 2021;51(4):728-734. doi: 10.1016/j.semarthrit.2021.04.012Casal-Dominguez M, Pinal-Fernandez I, Derfoul A, Graf R, Michelle H, Albayda J, et al. The phenotype of myositis patients with anti-Ku autoantibodies. Semin Arthritis Rheum. 2021;51(4):728-734. doi: 10.1016/j.semarthrit.2021.04.012Belizna C, Henrion D, Beucher A, Lavigne C, Ghaali A, Lévesque H. Anti-Ku antibodies: Clinical, genetic and diagnostic insights. Autoimmun Rev. 2010;9(10):691-694. doi: 10.1016/j.autrev.2010.05.020Belizna C, Henrion D, Beucher A, Lavigne C, Ghaali A, Lévesque H. Anti-Ku antibodies: Clinical, genetic and diagnostic insights. Autoimmun Rev. 2010;9(10):691-694. doi: 10.1016/j.autrev.2010.05.020Mimori T, Akizuki M, Yamagata H, Inada S, Yoshida S, Homma M. Characterization of a high molecular weight acidic nuclear protein recognized by autoantibodies in sera from patients with polymyositis – scleroderma overlap. J Clin Invest. 1981;68:611-620.Mimori T, Akizuki M, Yamagata H, Inada S, Yoshida S, Homma M. Characterization of a high molecular weight acidic nuclear protein recognized by autoantibodies in sera from patients with polymyositis – scleroderma overlap. J Clin Invest. 1981;68:611-620.Mimori T. Clinical significance of anti-Ku autoantibodies – A serologic marker of overlap syndrome? Intern Med. 2002;41(12): 1096-1098. doi: 10.2169/internalmedicine.41.1096Mimori T. Clinical significance of anti-Ku autoantibodies – A serologic marker of overlap syndrome? Intern Med. 2002;41(12): 1096-1098. doi: 10.2169/internalmedicine.41.1096Cooley HM, Melny BJ, Gleeson R, Greco T, Kay TW. Clinical and serological associations of anti-Ku antibody. J Rheumatol. 1999;26:563-567.Cooley HM, Melny BJ, Gleeson R, Greco T, Kay TW. Clinical and serological associations of anti-Ku antibody. J Rheumatol. 1999;26:563-567.Ghirardello A, Zampieri S, Iaccarino L, Tarricone E, Tonello M, Bendo R, et al. Gli anticorpi miosite specifici e miosite associati nelle miopatie infiammatorie idiopatiche: Studio sierologico di 46 pazienti [Myositis specific and myositis associated autoantibodies in idiopathic inflammatory myopathies: A serologic study of 46 patients]. Reumatismo. 2005;57(1):22-28. (In Italian). doi: 10.4081/reumatismo.2005.22Ghirardello A, Zampieri S, Iaccarino L, Tarricone E, Tonello M, Bendo R, et al. Gli anticorpi miosite specifici e miosite associati nelle miopatie infiammatorie idiopatiche: Studio sierologico di 46 pazienti [Myositis specific and myositis associated autoantibodies in idiopathic inflammatory myopathies: A serologic study of 46 patients]. Reumatismo. 2005;57(1):22-28. (In Italian). doi: 10.4081/reumatismo.2005.22Selva -O’Callaghan A, Labrador-Horrillo M, Solans-Laque R, Simeon-Aznar CP, Martínez-Gómez X, Vilardell-Tarrés M. Myositis-specific and myositis-associated antibodies in a series of eighty-eight Mediterranean patients with idiopathic inflammatory myopathy. Arthritis Rheum. 2006;55(5):791-798. doi: 10.1002/art.22237Selva -O’Callaghan A, Labrador-Horrillo M, Solans-Laque R, Simeon-Aznar CP, Martínez-Gómez X, Vilardell-Tarrés M. Myositis-specific and myositis-associated antibodies in a series of eighty-eight Mediterranean patients with idiopathic inflammatory myopathy. Arthritis Rheum. 2006;55(5):791-798. doi: 10.1002/art.22237Yaneva M, Arnett FC. Antibodies against Ku protein in sera from patients with autoimmune diseases. Clin Exp Immunol. 1989;76:366-372.Yaneva M, Arnett FC. Antibodies against Ku protein in sera from patients with autoimmune diseases. Clin Exp Immunol. 1989;76:366-372.McClain MT, Ramsland PA, Kaufman KM, James JA. Anti-Sm autoantibodies in systemic lupus target highly basic surface structures of complexed spliceosomal autoantigens. J Immunol. 2002;168(4):2054-2062. doi: 10.4049/jimmunol.168.4.2054McClain MT, Ramsland PA, Kaufman KM, James JA. Anti-Sm autoantibodies in systemic lupus target highly basic surface structures of complexed spliceosomal autoantigens. J Immunol. 2002;168(4):2054-2062. doi: 10.4049/jimmunol.168.4.2054Koenig M, Fritzler MJ, Targoff IN, Troyanov Y, Senécal JL. Heterogeneity of autoantibodies in 100 patients with autoimmune myositis: Insights into clinical features and outcomes. Arthritis Res Ther. 2007;9(4):R78. doi: 10.1186/ar2276Koenig M, Fritzler MJ, Targoff IN, Troyanov Y, Senécal JL. Heterogeneity of autoantibodies in 100 patients with autoimmune myositis: Insights into clinical features and outcomes. Arthritis Res Ther. 2007;9(4):R78. doi: 10.1186/ar2276Arnett FC, Targoff IN, Mimori T, Goldstein R, Warner NB, Reveille JD. Interrelationship of major histocompatibility complex class II alleles and autoantibodies in four ethnic groups with various forms of myositis. Arthritis Rheum. 1996;39(9):1507-1518. doi: 10.1002/art.1780390910Arnett FC, Targoff IN, Mimori T, Goldstein R, Warner NB, Reveille JD. Interrelationship of major histocompatibility complex class II alleles and autoantibodies in four ethnic groups with various forms of myositis. Arthritis Rheum. 1996;39(9):1507-1518. doi: 10.1002/art.1780390910Hirakata M, Mimori T, Akizuki M, Craft J, Hardin JA, Homma M. Autoantibodies to small nuclear and cytoplasmic ribonucleoproteins in Japanese patients with inflammatory muscle disease. Arthritis Rheum. 1992;35(4):449-456. doi: 10.1002/art.1780350415Hirakata M, Mimori T, Akizuki M, Craft J, Hardin JA, Homma M. Autoantibodies to small nuclear and cytoplasmic ribonucleoproteins in Japanese patients with inflammatory muscle disease. Arthritis Rheum. 1992;35(4):449-456. doi: 10.1002/art.1780350415Wang J, Satoh M, Kabir F, Shaw M, Domingo MA, Mansoor R, et al. Increased prevalence of autoantibodies to Ku antigen in African American versus white patients with systemic lupus erythematosus. Arthritis Rheum. 2001;44(10):2367-2370. doi: 10.1002/1529-0131(200110)44:10<2367::aid-art400>3.0.co;2-iWang J, Satoh M, Kabir F, Shaw M, Domingo MA, Mansoor R, et al. Increased prevalence of autoantibodies to Ku antigen in African American versus white patients with systemic lupus erythematosus. Arthritis Rheum. 2001;44(10):2367-2370. doi: 10.1002/1529-0131(200110)44:10<2367::aid-art400>3.0.co;2-iVillalta D, Tozzoli R, Tonutti E, Bizzaro N. The laboratory approach to the diagnosis of autoimmune diseases: Is it time to change? Autoimmun Rev. 2007;6(6):359-365. doi: 10.1016/j.autrev.2007.01.009Villalta D, Tozzoli R, Tonutti E, Bizzaro N. The laboratory approach to the diagnosis of autoimmune diseases: Is it time to change? Autoimmun Rev. 2007;6(6):359-365. doi: 10.1016/j.autrev.2007.01.009Franceschini F, Cavazzana I, Generali D, Quinzanini M, Viardi L, Ghirardello A, et al. Anti-Ku antibodies in connective tissue diseases: Clinical and serological evaluation of 14 patients. J Rheumatol. 2002;29:1393-1397.Franceschini F, Cavazzana I, Generali D, Quinzanini M, Viardi L, Ghirardello A, et al. Anti-Ku antibodies in connective tissue diseases: Clinical and serological evaluation of 14 patients. J Rheumatol. 2002;29:1393-1397.Spielmann L, Nespola B, Séverac F, Andres E, Kessler R, Guffroy A, et al. Anti-Ku syndrome with elevated CK and anti-Ku syndrome with anti-dsDNA are two distinct entities with different outcomes. Ann Rheum Dis. 2019;78(8):1101-1106. doi: 10.1136/annrheumdis-2018-214439Spielmann L, Nespola B, Séverac F, Andres E, Kessler R, Guffroy A, et al. Anti-Ku syndrome with elevated CK and anti-Ku syndrome with anti-dsDNA are two distinct entities with different outcomes. Ann Rheum Dis. 2019;78(8):1101-1106. doi: 10.1136/annrheumdis-2018-214439Lieber MR, Ma Y, Pannicke U, Schwarz K. The mechanism of vertebrate nonhomologous DNA end joining and its role in V(D)J recombination. DNA Repair. 2004;3:817-826.Lieber MR, Ma Y, Pannicke U, Schwarz K. The mechanism of vertebrate nonhomologous DNA end joining and its role in V(D)J recombination. DNA Repair. 2004;3:817-826.Schild-Poulter C, Su A, Shih A, Kelly OP, Fritzler MJ, Goldstein R, et al. Association of autoantibodies with Ku and DNA repair proteins in connective tissue diseases. Rheumatology (Oxford). 2008;47(2):165-171. doi: 10.1093/rheumatology/kem338Schild-Poulter C, Su A, Shih A, Kelly OP, Fritzler MJ, Goldstein R, et al. Association of autoantibodies with Ku and DNA repair proteins in connective tissue diseases. Rheumatology (Oxford). 2008;47(2):165-171. doi: 10.1093/rheumatology/kem338Rigolet A, Musset L, Dubourg O, Maisonobe T, Grenier P, Charuel JL, et al. Inflammatory myopathies with anti-Ku antibodies: A prognosis dependent on associated lung disease. Medicine (Baltimore). 2012;91(2):95-102. doi: 10.1097/MD.0b013e31824d9cecRigolet A, Musset L, Dubourg O, Maisonobe T, Grenier P, Charuel JL, et al. Inflammatory myopathies with anti-Ku antibodies: A prognosis dependent on associated lung disease. Medicine (Baltimore). 2012;91(2):95-102. doi: 10.1097/MD.0b013e31824d9cecKishi T, Miyamae T, Morimoto R, Ishiguro N, Hamaguchi Y, Fujimoto M, et al. Childhood-onset anti-Ku antibody-positive generalized morphea with polymyositis: A Japanese case study. Pediatr Dermatol. 201532(5):e224-e225. doi: 10.1111/pde.12644Kishi T, Miyamae T, Morimoto R, Ishiguro N, Hamaguchi Y, Fujimoto M, et al. Childhood-onset anti-Ku antibody-positive generalized morphea with polymyositis: A Japanese case study. Pediatr Dermatol. 201532(5):e224-e225. doi: 10.1111/pde.12644Meek K, Gupta S, Ramsden DA, Lees-Miller SP. The DNAdependent protein kinase: The director at the end. Immunol Rev. 2004;200:132-141. doi: 10.1111/j.0105-2896.2004.00162.xMeek K, Gupta S, Ramsden DA, Lees-Miller SP. The DNAdependent protein kinase: The director at the end. Immunol Rev. 2004;200:132-141. doi: 10.1111/j.0105-2896.2004.00162.xBohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975;292:344-347.Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975;292:344-347.van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall L, et al. 2013 classification criteria for systemic sclerosis: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2013;72(11):1747-1755. doi: 10.1136/annrheumdis-2013-204424van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall L, et al. 2013 classification criteria for systemic sclerosis: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2013;72(11):1747-1755. doi: 10.1136/annrheumdis-2013-204424Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, et al. 2016 American College of Rheumatology/ European League Against Rheumatism classification criteria for primary Sjögren’s syndrome: A consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol. 2017;69(1):35-45. doi: 10.1002/art.39859Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, et al. 2016 American College of Rheumatology/ European League Against Rheumatism classification criteria for primary Sjögren’s syndrome: A consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol. 2017;69(1):35-45. doi: 10.1002/art.39859Fredi M, Cavazzana I, Quinzanini M, Taraborelli M, Cartella S, Tincani A, et al. Rare autoantibodies to cellular antigens in systemic lupus erythematosus. Lupus. 2014;23(7):672-677. doi: 10.1177/0961203314524850Fredi M, Cavazzana I, Quinzanini M, Taraborelli M, Cartella S, Tincani A, et al. Rare autoantibodies to cellular antigens in systemic lupus erythematosus. Lupus. 2014;23(7):672-677. doi: 10.1177/0961203314524850Ho KT, Reveille JD. The clinical relevance of autoantibodies in scleroderma. Arthritis Res Ther. 2003;5(2):80-93. doi: 10.1186/ar628Ho KT, Reveille JD. The clinical relevance of autoantibodies in scleroderma. Arthritis Res Ther. 2003;5(2):80-93. doi: 10.1186/ar628Cavazzana I, Ceribelli A, Quinzanini M, Scarsi M, Airò P, Cattaneo R, et al. Prevalence and clinical associations of anti-Ku antibodies in systemic autoimmune diseases. Lupus. 2008;17(8):727-732. doi: 10.1177/0961203308089442Cavazzana I, Ceribelli A, Quinzanini M, Scarsi M, Airò P, Cattaneo R, et al. Prevalence and clinical associations of anti-Ku antibodies in systemic autoimmune diseases. Lupus. 2008;17(8):727-732. doi: 10.1177/0961203308089442Hoa S, Hudson M, Troyanov Y, Proudman S, Walker J, Stevens W, et al. Single-specificity anti-Ku antibodies in an international cohort of 2140 systemic sclerosis subjects: Clinical associations. Medicine (Baltimore). 2016;95(35):e4713. doi: 10.1097/MD.0000000000004713Hoa S, Hudson M, Troyanov Y, Proudman S, Walker J, Stevens W, et al. Single-specificity anti-Ku antibodies in an international cohort of 2140 systemic sclerosis subjects: Clinical associations. Medicine (Baltimore). 2016;95(35):e4713. doi: 10.1097/MD.0000000000004713

The authors declare that there are no conflicts of interest present.